Point-of-care fresh CAR T cells for pediatric or young adult BCP-ALL that is relapsed/refractory or in very-high-risk first relapse.
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The point-of-care, automated manufacturing of chimeric antigen receptor (CAR) T cells can reduce the waiting window and increase the therapy accessibility to patients with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) as compared with commercially available drug products (DPs). We conducted a phase 1/2 trial (NCT04787263) on the use of second-generation (4.1BB), CD19-CAR T cells, for the treatment of patients with BCP-ALL with either first relapse and very-high-risk (VHR) characteristics or second/subsequent relapse and rapidly progressing disease. CAR T cells were manufactured with a 12-day process using CliniMACS Prodigy, from a fresh apheresis and infused fresh. Three dose levels were tested in the phase 1: 1.0, 2.0, and 3.0×106 CAR+ T cells/kg. Nineteen patients were enrolled, 13 (68%) in first VHR relapse. The designed dose was always successfully produced. No dose-limiting toxicities were observed in the phase 1. Grade 1 to 2 cytokine release syndrome was observed in 13 (68%) patients. Grade 1 to 2 immune effector cell-associated neurotoxicity syndrome occurred in 2 patients and resolved spontaneously. All patients achieved bone marrow complete remission (CR) with negative minimal residual disease. Eight patients (42%) received hematopoietic stem cell transplantation (HSCT) consolidation. Overall, CR was maintained in 13 of 19 patients (68%), 7 of whom having received HSCT. Importantly, all but 1 patient treated with 3.0×106 CAR+ T cells/kg maintained CR. The 3-year event-free survival and overall survival of the whole cohort are 68% and 83%, respectively. Our data suggest that the point-of-care manufacturing of autologous, anti-CD19 CAR T cells can successfully treat patients with BCP-ALL including those with first relapse and VHR characteristics.